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Flashcards in Peter Browlett Lectures Deck (99):
1

what is haematopoesis

Process by which mature blood cells are generated
from stem cells in the bone marrow

2

Why do we need to study
haematopoiesis ?

blood tests are important part of management of patients

3

definition of haematopoetic tissue and 2 main examples

tissues generating non-lymphoid cells of the blood
- bone marrow (mainly sternum)
- spleen

4

what are the haematopoetic sites during development?

yolk sac, AGM endothelium and placenta --> fetal liver --> bone marrow

5

changes in bone marrow of distal bones with age

during childhood there is progressive fatty replacement of marrow thoughout the long bones, the fatty tissue can revert back to haematopoetic tissue

6

what is extramedullary haematopoiesis, when is this observed?

haematopoesis in the organs other than bone marrow, e.g. spleen or liver. Can be observed in diseased states

7

what is myelofibrosis

type of myeloproliferative neoplasm- abnormal clone of HPSC - resulting in fibrosis (or replacement wiht scar tissue)

8

what are the main constituents of bone marrow?

trabecular bone

fat cells (stromal cells)

HPSC

9

changes to the cellularity of bone marrow with age

decrease

10

decribe the hierachy of the haematopoesis

stem cells generate progenitor cells (lymphoid and myeloid)

11

what antigen is used to measure stem cells

CD34 antigen is expressed on the human HSC

12

3 sources of HSCs

Bone marrow

umbilical cord

peripheral blood

13

function of erythropoetin

stimulate RBC production

14

function of thrombopoetin

stimulates platelet production

15

function of granulocyte colony stimulating factor

stimulates neutrophil production

16

3 Assessment of Blood & Bone
Marrow

full blood count (automated, gives absollute nyumbers and cell types - impt to look at morphology)

bone marrow examination - HSC

stem cells - look for CD34 positive cells

17

what is acute myeloid leukemia
- symptoms
- diagnosis
- treatment

cancer of the myeloid line of blood cells - rapid growth of abnormal cells.
- tiredness, bruising and easy infections

- diagnosis by decrease RBC and platelets, bone marrow examination

- treatment by chemotherapy and supportive care, antibiotics to prevent infections.

18

the shape of a RBC allows for

flexibility
increased area for gas exchange

19

function of RBC

Hb carriage
O2 transport

20

what is hereditary spherocytosis

abnormality in the membrane of RB causing shortened lifespan of the RBC

21

the RBC keeps the Hb in a ___ ____ and maintains _______ ________

reduced state

osmotic equilibrium

22

what is G6PD deficiency?

inherited defects in enzyme pathways causing haemolysis (shortened RBC survival)

23

basic structure of haemoglobin

2 alpha globulin chains and 2 beta globulin chains and haem group

24

how does iron deficiency cause anaemia?

reduced production of haem due to low iron

25

how do thalassaemias cause anaemia

impaired production of globin chains- results in low Hb

26

what are the 4 morhological stages of erythroid precursor cell differentiation?

progressice increase in Hb

chromatin clumping

extrude nucelus

loss of RNA

27

average lifespan of RBC

120 days

28

main regulator of erythropoesis
- where is this produced
- what triggers production?

erythropoetin
- produced in kidneys
- responds to low O2 tensions (increase EPO production)

29

what are 4 effects of EPO?

binds to the EPO receptor
- stimulates RBC progenitor cells
- increased Hb synthesis
- reduced RBC maturation time
- increased reticulocyte release

30

when is clinical use of recombinant EPO?

anaemia of renal failure
- also myelodysplastic syndromes

31

process of RBC destruction- what are the end products?

RBC breakdown in the liver by macrophages

- Hb is broken down into haem and globin chains

haem:
- iron --> bone marrow
- protoporphyrin - bilirubin (liver-bile)

32

definition of anaemia

low Hb than normal for the age and sex patient

33

cardiovascular responses to anaemia

increased cardiac output (right shift in Hb dissociation curve)
- makes O2 more readily available to tissues

34

difference between physiological and morphological classifications of anaemia?

physiological- impaired production or increased loss/reduced survival

morphological- based on the appearance and size of cells (microcytic/macrocytic)

35

2 categories of physiological anaemia?

ineffecitve production or decreased RBC survival

36

3 main causes of impaired RBC production

decifiencies (B12, folate, iron)

genetic defect in produciton (thalassaemia)

bone marrow failure (leukemia, irradiation or drugs)

37

2 cause so freduced RBC survival

blood loss (trauma or surgery)

haemolysis

38

what parameters are used to differentiate morphological anaemias?

MCV, Hb concentration and blood film observations

39

what is the haematocrit

the ratio of colume of RBC to the total volume of blood

40

3 causes of microcytic hypochromic (reduced Hb) anaemia

iron deficiency

chronic illness (iron block)

genetic - thalassaemia

41

what are the 4 ways to diagnose iron deficiency?

measure serum iron, iron binding capacity (transferrin) and iron saturation, serum ferritin

42

what does serum iron measure?

measures the amount of iron in the liquid portion of the blood

43

what does transferrin measure?

directly measures the level of transferrin in the blood. Transferrin is the protein that transports iron around in the body. Under normal conditions, transferrin is typically one-third saturated with iron. This means that about two-thirds of its capacity is held in reserve

44

what does serum ferritin measure?

reflects the amount of stored iron int he body

45

what does TIBC measure?

(total iron-binding capacity)—measures the total amount of iron that can be bound by proteins in the blood. Since transferrin is the primary iron-binding protein, the TIBC test is a good indirect measurement of transferrin availability.

46

what does UIBC measure?

(unsaturated iron-binding capacity)—The UIBC test determines the reserve capacity of transferrin, i.e., the portion of transferrin that has not yet been saturated with iron. UIBC also reflects transferrin levels.

47

what does Transferrin saturation measure?

a calculation that reflects the percentage of transferrin that is saturated with iron (100 x serum iron/TIBC)

48

Iron is normally absorbed from food in the ____ ______ and transported throughout the body by binding to ________, a protein produced by the _____. In healthy people, most of the iron transported is incorporated into the production of ________. The remainder is stored in the tissues as ______.

Iron is normally absorbed from food in the small intestine and transported throughout the body by binding to transferrin, a protein produced by the liver. In healthy people, most of the iron transported is incorporated into the production of hemoglobin. The remainder is stored in the tissues as ferritin.

49

what is haemachromatosis?

rare genetic disease in which the body absorbs and builds up too much iron, even on a normal diet.

50

serum iron, UIBC and serum feritin levels in iron deficiency

increased UIBC and decreased SF

51

serum iron, saturation, TIBC and serum feritin levels in anaemia of chronic disease (inflammation)

ferritin is normal or high (ferritin is a acute phase protein)

normal or slightly decreased serum iron and TIBC

normal saturation

52

why is ferritin known as a acute phase protein? why does this increase with chronic disease

increases with inflammation
- liver damage can cause ferritin to leak out
- also in hodgkins lymphoma

53

4 causes of iron deficiency

diet (vegetarian)

malabsoprtion (proximal small bowel)

increased demands (pregnancy)

chronic blood loss (GI tract malignancy)

54

what are the 2 forms of iron replacement therapy? example for each?

oral= ferogradumet
IV= ferric carboxymatlose

55

what is hepcidin, why is it high during inflammation and what are the downstream effects?

regulator of entry of iron into the bloodstream
- inflammation causes high hepcidin, serum iron falls due to iron trapping within the macrophages and liver cells + decreased gut iron absoprtion.

this causes iron deficiency and hence anaemia

56

RBC cellular characteristics of beta thalassaemia

fragmented or irregular shaped RBC

Small or microcytic RBC

57

diagnosis of thalassaemia

blood counts (Hb, MCV and RBC counts)
- iron studies and phenotypic analysis

58

5 main causes of macrocytic anaemia

B12/folate def
alcohol
liver disease
primary bone marrow disorders
hypothyroidism

59

example of macrocytic megaloplastic anaemia cause- what is the mechanism?

B12/folate deificiency
- impaired DNA synthesis

60

causes of low B12/folate

diet - vegans (B12 is in milk, eggs and meat)
malabsorption
- gastrectomy
- immune (pernicious anaemia)
- terminal ileum disease

61

why do B12 deficiencies present late?

the body has stores of B12 for 3-4 years

62

causes of low folate

lack of veges

coeliac

increased demands (pregnancy)

63

2 types of haemolytic anaemia

intrinsic = inherited defect in the RBC membrane

extrinsic = autoimmune

64

clinical presentation of haemolytic anaemia

anaemia

jaundice, splenomegaly

raised reticulocyte count (due to increased production)

65

what are the 2 main types of leukocytes?

phagocytes

lymphocytes

66

sub-categories of phagocytes and examples

granulocytes (neutrophils-90%, eosino and basophils)

monocytes

67

describe teh kinetics of granulocyte production?
- maturation time
- circulating time

7-10 day maturation
6-10 hours circulation before entering tissues for phagocytosis

68

main regulators of granulopoiesis

haematopoetic growth factors
(IL3, stem cell factor, G-CSF)

69

what is G-CSF, (brand name) and effects- who is it used for?

granulocyte colony stimulating factor (filgastrim)
- used in patients with neutropenia (bone marrow failure, chemotherapy)

70

3 functions of neutrophils

chemotaxis

phagocytosis

killing bacteria
- (non)/oxidative

71

what is Neutrophil leucocytosis

increased number of neutrophils usually due to inflammation or infection

72

what is neutropenia, what are the risks (what is this called?)

patients with a low neutrophil count
- have an increased risk of infection
--> febrile neutropenia

73

which of the phagocytes are granulocytes?

neutrophils
eosinophils
basophils

74

process of monocyte development

circulate for 1-3 days
- enter tissues (transform into macrophages)

75

what are the main phagocytic functions of monocytes?

chemotaxis
opsonisation
phagocytosis (and ingestion)

76

what are the 3 main roles of the monocytes?

phagocytosis
synthetic functions (complement, interferon)
antigen presentation

77

what is monocytosis? what are the 2 types? examples?

monocytosis- increased
- reactive= chronic infections (TB)

- malignant- acute/chronic myeloid leukemia (monoblastic type)

78

what is Eosinophilia and when is this observed?

increase in eosinophils- allergy/hypersensitivity reactions
also parasite infections

79

effects and function of basophils

close relationship to mast cells
- allergic symtpoms
granules contain histamine (vasoldilation)

80

what is the normal make up of citculating lymphocytes? (%)

75% ish T cells
10% B cells
NK cells

81

what are primary lymphoid organs and examples for B cells and T cell?

where lymphocytes are formed and mature
B= Bone marrow
T= Thymus

82

what are Secondary Lymphoid Organs
and examples?

where lymphocytes are activated
- lymph nodes
spleen
bone marrow

83

what are the 2 potential classifications of causes of lymph node enlargement?

reactive - viral/bacterial infection

malignancy- lymphomas or metastatic spread

84

causes of Lymphocytosis

reactive - viral (infectious mononucelosis)

malignant - chronic lymphocytic leukemia

85

Lymphopenia causes?

HIV infections (CD4 T cell deficit)
- steroid therapy, bone marrow failure

86

define Polycythaemia

state of disease where haematocrit is increased

87

4 mains types of blood and bone marrow cancers

leukemia

myeloproloferative neoplasms

lymphomas

myeloma

88

what is the pathological process of leukemia

proliferation of immature bone marrow cells (lose abiloity to differentiate beyond "blast" cells)

- expand tha replace normal cells
- abnormal leukemic cells spill into the blood.

89

4 pathogenesis causes of leukemia?

congenital/inherited

viral infections

radiation

chemical/DNA changing drugs

90

2 subtypes of acute leukemia?

acute myeloid leukemia (AML)

Acute lymphoblastic leukemia (ALL)

91

2 types of leukemia?

acute, chronic

92

what are the 3 main clinical symptoms of Acute leukemia?
what are some less common symptoms?

loss on normal cells (RBC, platelets and neutrophils)
- fatigue (anaemia), bleeding (thrombocytopenia) and infections (neutropenia)

liver and spleen enlargement
bone pain (marrow infiltration)

93

what ages are acute leukemia likely to present?

occur over all ages
- ALL - mainly childhood
AML - mainly adults

94

how is leukemia diagnosed?

full blood count
bone marrow biopsy

95

blood count results of leukemia

full blood count
- anaemia
- WBC increase
- usually severe thrombocytopenia

96

bone marrow biopsy indications of leukemia

over 20% blasts (myeloid or lymphoid)

97

treatment for acute leukemia

general/supportive care:
- infusion (RBC and platelets)
managing infections (antibiotics)

chemotherapy

HSC transplant

98

what are the 3 steps of acute leukemia chemotherapy?

Induction therapy- lower the number of plasma cells in bone marrow (induce remission)

consolidation- to mop up residual leukaemia
cells

maintainance therapy (only ALL)- keep patients in remission

99

what is autologous and allogenic HSC transplant?

autologous- own stem cells are taken in remission

allogenic- matched sibling or unrelated donor